The effectiveness of nicotine replacement therapy on oral smokelesstobacco cessation and reduction rate: A systematic review

Nicotine replacement therapy for smoking cessation in the “real world”

IntroductionThe effectiveness of nicotine replacement therapy (NRT) on smokeless tobacco (SLT) users is underexplored in India, with prior research primarily focusing on smokers. This study assessed and compared the effectiveness of combining behavioral intervention (BI) and NRT with BI alone on smoking and SLT cessation.MethodsThis 1.5-year prospective, open-label, three-arm parallel-group randomized controlled trial was conducted at the Tobacco Cessation Clinic, SCB Dental College and Hospital, Odisha, India. The three intervention groups—BI, BI + nicotine patch, and BI + nicotine gum—were assessed using a prevalidated proforma on sociodemographics, relevant medical and dental history, oral hygiene practices, and previous tobacco use patterns.ResultsThe study enrolled 130 participants. At 26 weeks, 63.3% (19/30) in the BI + patch and 52.9% (18/34) in the BI + gum achieved abstinence, compared to 24.1% (7/29) in the BI group. The odds ratio (OR), 95% confidence interval (CI); p-value of abstinence was 6.03 (1.90–19.15; p = .003) for BI + patch, and 3.25 (1.08–9.78; p = .035) for BI + gum. Among SLT users, abstinence was achieved in 70.59% (12/17) with BI + patch (OR 6.40, 95% CI: 1.57–26.03; p = .010) and 53.85% (14/26) with BI + gum (OR 3.11, 95% CI: .92–10.47; p = .067) versus 27.27% (6/22) with BI alone. Both intervention groups demonstrated significantly reduced relapse risk versus BI alone (Hazard ratio [HR] 0.45, 95% CI: .24–.83; p = .011) for BI + patch and HR 0.40, 95% CI: .22–.74; p = .003 for BI + gum.ConclusionCombination therapy (BI + NRT) is more effective than BI alone. The BI + patch combination is more effective than BI + gum and BI alone. The NRT intervention groups had higher abstinence rates and reduced relapses than the standard BI group. Further studies are required to validate these findings.

The aim of nicotine replacement therapy (NRT) is to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. The aims of this review were: To determine the effect of NRT compared to placebo in aiding smoking cessation, and to consider whether there is a difference in effect for the different forms of NRT (chewing gum, transdermal patches, oral and nasal sprays, inhalers and tablets/lozenges) in achieving abstinence from cigarettes. To determine whether the effect is influenced by the dosage, form and timing of use of NRT; the intensity of additional advice and support offered to the smoker; or the clinical setting in which the smoker is recruited and treated. To determine whether combinations of NRT are more likely to lead to successful quitting than one type alone. To determine whether NRT is more or less likely to lead to successful quitting compared to other pharmacotherapies. We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search July 2012. Randomized trials in which NRT was compared to placebo or to no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. We extracted data in duplicate on the type of participants, the dose, duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. We identified 150 trials; 117 with over 50,000 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The risk ratio (RR) of abstinence for any form of NRT relative to control was 1.60 (95% confidence interval [CI] 1.53 to 1.68). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 55 trials) for nicotine gum; 1.64 (95% CI 1.52 to 1.78, 43 trials) for nicotine patch; 1.95 (95% CI 1.61 to 2.36, 6 trials) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials) for nicotine inhaler; and 2.02 (95% CI 1.49 to 2.73, 4 trials) for nicotine nasal spray. One trial of oral spray had an RR of 2.48 (95% CI 1.24 to 4.94). The effects were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. The effect was similar in a small group of studies that aimed to assess use of NRT obtained without a prescription. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2 mg gum, but weaker evidence of a benefit from higher doses of patch. There was evidence that combining a nicotine patch with a rapid delivery form of NRT was more effective than a single type of NRT (RR 1.34, 95% CI 1.18 to 1.51, 9 trials). The RR for NRT used for a short period prior to the quit date was 1.18 (95% CI 0.98 to 1.40, 8 trials), just missing statistical significance, though the efficacy increased when we pooled only patch trials and when we removed one trial in which confounding was likely. Five studies directly compared NRT to a non-nicotine pharmacotherapy, bupropion; there was no evidence of a difference in efficacy (RR 1.01; 95% CI 0.87 to 1.18). A combination of NRT and bupropion was more effective than bupropion alone (RR 1.24; 95% CI 1.06 to 1.45, 4 trials). Adverse effects from using NRT are related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. There is no evidence that NRT increases the risk of heart attacks. All of the commercially available forms of NRT (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50 to 70%, regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT.

The effectiveness of nicotine replacement therapy (NRT) in critically ill patients remains uncertain, as conflicting research results have been reported. Despite potential side effects and inconsistent data on safety and efficacy, NRT is still prescribed in intensive care units (ICUs) to prevent withdrawal symptoms and manage agitation in patients who are smokers. This meta-analysis aimed to assess the effectiveness of nicotine replacement therapy in critically ill smoking patients. A systematic review and meta-analysis of randomized controlled trials investigated the outcomes of smokers admitted to ICUs and were randomized either to receive or not receive nicotine replacement therapy (NRT) during their ICU stay. The MEDLINE and Embase databases were searched from inception through 13 February 2023 using OVID. The primary outcome was ICU length of stay (LOS) for this systematic review and meta-analysis. Meta-analysis was conducted using both random-effects and fixed-effect models; the latter is recommended when meta-analysis is restricted to just a few studies. The study was registered in the Prospective International Register of Systematic Reviews (PROSPERO) under reference number CRD42023407804. Of 28 studies initially identified, three, with 67 patients on NRT and 72 controls, were deemed eligible for pooled analysis. Patients who received NRT experienced a shorter LOS (mean difference, MD= -3.06; 95% CI: -5.88 - -0.25, p=0.0, I2=0%). The mechanical ventilation (MV) duration was also shorter in the NRT group, but this difference was not statistically significant (MD= -1.24; 95% CI: -3.21-0.72, p=0.22, I2=12.69%). Delirium duration was reported by two studies, from which pooled analysis revealed an MD of -0.50 (95% CI: -1.63-0.62, I2=0%). The vasopressor duration was assessed in two studies, and the overall MD for vasopressor duration was not statistically different between NRT patients and controls in the fixed-effects model (MD=0.11; 95% CI: -0.75-0.96, I2=0%). Critically ill smoker patients who received NRT experienced a significantly shorter ICU LOS but no significant differences in the durations of MV, vasopressor use, or delirium.

This open study assessed the effects of nicotine replacement therapy (NRT) on the normalizing of exhaled carbon monoxide (CO), transcutaneous partial oxygen tension (tcpO(2)), plasma cotinine and thiocyanate levels, and cardiovascular risk markers in abstinent subjects compared with untreated smokers after 4, 8, 12, and 26 weeks. The trial enrolled 197 subjects in two parallel groups: 164 subjects who received NRT (patch plus gum) for 12 weeks and 33 untreated smokers (controls). At 26 weeks, 123/164 participants in the treatment group had completed the study; 51/123 (41.5%) sustained abstinence from smoking, whereas 72/123 (58.5%) had relapsed. Changes in cotinine (abstainers: 291.6 ng/ml at baseline vs. 27.3 ng/ml at week 26; p<.0001) and thiocyanate levels (abstainers: 10.4 ng/ml at baseline vs. 6.2 ng/ml at week 26; p<.0001) and expired CO (abstainers: 30.4 ppm at baseline vs. 4.2 ppm at week 26; p<.0001) accurately reflected the changes in smoking and/or NRT use in both abstainers and relapsers. After they stopping smoking, tcpO(2) significantly improved in abstainers (34.9 mmHg at baseline vs. 50.4 mmHg at week 26; p<0.0001). Inverse correlations between the number of daily cigarettes and plasma cotinine, thiocyanate, and exhaled CO levels were observed in both relapsers and smokers. A clinically significant increase in HDL cholesterol (39.0 vs. 44.7 mg/dl; p<.0001) occurred in the abstainers between baseline and study end. Use of combination NRT to achieve abstinence resulted in marked improvements in biochemical parameters in abstainers and partial improvements in relapsers. The safety of combination NRT was confirmed by the absence of overdose-related adverse events.

This open study assessed the effects of nicotine replacement therapy (NRT) on the normalizing of exhaled carbon monoxide (CO), transcutaneous partial oxygen tension (tcpO 2 ), plasma cotinine and thiocyanate levels, and cardiovascular risk markers in abstinent subjects compared with untreated smokers after 4, 8, 12, and 26 weeks. The trial enrolled 197 subjects in two parallel groups: 164 subjects who received NRT (patch plus gum) for 12 weeks and 33 untreated smokers (controls). At 26 weeks, 123/164 participants in the treatment group had completed the study; 51/123 (41.5%) sustained abstinence from smoking, whereas 72/123 (58.5%) had relapsed. Changes in cotinine (abstainers: 291.6 ng/ml at baseline vs. 27.3 ng/ml at week 26; p<.0001) and thiocyanate levels (abstainers: 10.4 ng/ml at baseline vs. 6.2 ng/ml at week 26; p<.0001) and expired CO (abstainers: 30.4 ppm at baseline vs. 4.2 ppm at week 26; p<.0001) accurately reflected the changes in smoking and/or NRT use in both abstainers and relapsers. After they stopping smoking, tcpO2 significantly improved in abstainers (34.9 mmHg at baseline vs. 50.4 mmHg at week 26; p<0.0001). Inverse correlations between the number of daily cigarettes and plasma cotinine, thiocyanate, and exhaled CO levels were observed in both relapsers and smokers. A clinically significant increase in HDL cholesterol (39.0 vs. 44.7 mg/dl; p<.0001) occurred in the abstainers between baseline and study end. Use of combination NRT to achieve abstinence resulted in marked improvements in biochemical parameters in abstainers and partial improvements in relapsers. The safety of combination NRT was confirmed by the absence of overdose-related adverse events.

This paper examines the effect of nicotine replacement therapy (NRT) advertising on youth smoking. NRT advertising could decrease smoking by informing smokers that the product can make quitting easier and thus inducing more smokers to try and quit. However, a moral hazard is created because NRT advertising increases the expectation that cessation is relatively easy. NRT advertising could thus induce youth to smoke, to smoke more and/or to delay quit attempts. Data from Nielsen Media Research (Nielsen) and the Monitoring the Future Surveys (MTF) have been used in the empirical work. The Nielsen data are matched to the MTF data by month, year and market. The availability of lagged advertising data allow for calculation of an advertising stock variable. The Nielsen data also measure exposure to national advertising on a local level which allows for use of national advertising data. An exogenous shock allows for bypassing problems of endogeneity. The results indicate that NRT advertising has no effect on participation but increases smoking by youth who do smoke. The elasticity of smoking with respect to NRT advertising is about .10 and the elasticity of smoking with respect to price is about -1.03. Since average youth smoking is about 5.77 cigarettes per day, an increase of 10 percent in NRT advertising would increase this average to about 5.82 cigarettes per day. It is also estimated that a ban on NRT advertising would be equivalent to a 10 percent increase in cigarette prices.

Is nicotine replacement really ineffective? A reply to Stanley and Massey

BackgroundThe effectiveness of Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy is limited by inconsistent and incorrect use. This paper describes the development process for “Baby, Me, & NRT”, a novel pregnancy-specific intervention aimed at enhancing adherence to NRT.MethodsAn integrated approach to intervention development was used, combining evidence, theory, stakeholders’ feedback, and tailoring principles. The process involved six iterative steps: (1) synthesizing relevant published evidence and guidance, (2) collecting primary qualitative data on barriers and facilitators to NRT adherence along with potential intervention design features, (3) identifying relevant behavioral theories and mapping the evidence against these, (4) prioritizing behavioral determinants identified in steps 1 and 2, generating intervention objectives, and identifying behavior change techniques which target the prioritized determinants, (5) consulting with stakeholders on intervention components, key content and tailoring features, and (6) producing a prototype intervention along with implementation guidance.ResultsThe prototype intervention comprises of a multi-component, 1-month cessation programme, which includes six enhanced behavioral support sessions delivered by a trained advisor, tailored text messages, a website, and an illustrated booklet. It promotes the uptake of high-dose and combination NRT, emphasizes the importance of adherence, addresses motivation to use NRT, proactively helps problem solve NRT use issues, and provides guidance on preventing and managing smoking lapses.ConclusionThe development process generated an evidence- and theory-guided intervention, designed with stakeholder input, aimed at improving NRT effectiveness for smoking cessation in pregnancy. The prototype intervention has since been optimized and is being evaluated in a randomized controlled trial.

BackgroundResearch is inconclusive on the effectiveness of electronic nicotine delivery systems (ENDS) as cigarette cessation aids compared with nicotine replacement therapy (NRT) or non-NRT medication. This study compared the cigarette...

To describe the effect of nicotine replacement therapy (NRT) on the risk of relapse as a function of time since the quit date. Meta-analysis of 21 published, randomized, controlled clinical trials, comparing NRT to placebo. A total of 6644 smokers were treated with NRT and 2766 smokers treated with placebo. During treatment with the medication, NRT reduced the hazard ratio (HR) significantly compared with placebo [early HR = 0.62 (95% CI: 0.58-0.67)]. At the end of the average treatment duration (145 days), the HR was 0.81 (95% CI: 0.71-0.94), showing that the benefit was still present at this time. After stopping treatment, the HR increased progressively up to a value of 1.44 (95% CI, 1.18-1.76) showing that the risk of relapse was higher after stopping NRT than after stopping placebo. If NRT and placebo had not been stopped, the HR of smoking relapse would have been established at 0.95 (95% CI: 0.76-1.18, P = 0.64), indicating a similar risk of relapse with NRT and placebo. Moreover, the observed HR of smoking relapse was significantly higher than the expected HR of smoking relapse if NRT had been continued: the difference in HR is 1.51 (95% CI: 1.16-1.98, P < 0.003). This suggests that if NRT had been been continued, around 50% of relapses could have been prevented. The protective effect of NRT against relapse slowly decreases as a function of time. After stopping NRT, the risk of relapse increases. It may be more beneficial not to stop NRT after the usual 3-6-month treatment period but to use NRT for longer periods of time.

Nicotine Replacement Therapy

To review data assessing the effects of nicotine replacement therapy (NRT) during pregnancy on fetal, neonatal, and maternal outcomes. A literature search of PubMed (1966-July 2010) was performed using the terms smoking, smoking cessation, pregnancy, and nicotine replacement therapy. Bibliographies and the Cochrane Database were reviewed to identify additional relevant articles. All studies including humans and published in English with data describing NRT effects on pregnancy outcomes or malformations as a primary or secondary outcome were evaluated. Currently, behavior modification therapy is recommended for smoking cessation in pregnancy as first-line treatment, but NRT should be offered to patients who are not successful. NRT is currently a pregnancy category D medication. Pregnancy outcomes and malformation rates for NRT in pregnancy were evaluated as either primary or secondary outcomes in several trials. Four studies examined pregnancy outcomes after a full course of nicotine gum or patch therapy. NRT use significantly decreased the risk of preterm delivery and low birth weight compared to that of smokers. Only 1 study evaluated the risk of malformations after exposure to the NRT patch during the first trimester. In a retrospective analysis, NRT users had an increased risk for any fetal malformation but not for major or musculoskeletal ones. However, no adjustments were made for many known factors associated with malformations. Behavior modification therapy should always be the first method tried for smoking cessation in the pregnant population. If behavior modification therapy is attempted without success, NRT should be offered because of decreased risk for low birth weight and preterm delivery compared to continued smoking. Additionally, NRT does not appear to increase the risk for malformations.

The aim of nicotine replacement therapy (NRT) is temporarily to replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. The aims of this review were:To determine the effect of NRT compared to placebo in aiding smoking cessation, and to consider whether there is a difference in effect for the different forms of NRT (chewing gum, transdermal patches, nasal spray, inhalers and tablets/lozenges) in achieving abstinence from cigarettes. To determine whether the effect is influenced by the dosage, form and timing of use of NRT; the intensity of additional advice and support offered to the smoker; or the clinical setting in which the smoker is recruited and treated. To determine whether combinations of NRT are more likely to lead to successful quitting than one type alone. To determine whether NRT is more or less likely to lead to successful quitting compared to other pharmacotherapies. We searched the Cochrane Tobacco Addiction Group trials register for papers with 'nicotine' or 'NRT' in the title, abstract or keywords. Date of most recent search July 2007. Randomized trials in which NRT was compared to placebo or to no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow up of less than six months. We extracted data in duplicate on the type of participants, the dose, duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was abstinence from smoking after at least six months of follow up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. We identified 132 trials; 111 with over 40,000 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The RR of abstinence for any form of NRT relative to control was 1.58 (95% confidence interval [CI]: 1.50 to 1.66). The pooled RR for each type were 1.43 (95% CI: 1.33 to 1.53, 53 trials) for nicotine gum; 1.66 (95% CI: 1.53 to 1.81, 41 trials) for nicotine patch; 1.90 (95% CI: 1.36 to 2.67, 4 trials) for nicotine inhaler; 2.00 (95% CI: 1.63 to 2.45, 6 trials) for oral tablets/lozenges; and 2.02 (95% CI: 1.49 to 3.73, 4 trials) for nicotine nasal spray. The effects were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. The effect was similar in a small group of studies that aimed to assess use of NRT obtained without a prescription. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2 mg gum, but weaker evidence of a benefit from higher doses of patch. There was evidence that combining a nicotine patch with a rapid delivery form of NRT was more effective than a single type of NRT. Only one study directly compared NRT to another pharmacotherapy. In this study quit rates with nicotine patch were lower than with the antidepressant bupropion. All of the commercially available forms of NRT (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50-70%, regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT.

AimsThis systematic review aims to evaluate the effect of nicotine replacement therapies (NRTs) on measures of agitation amongst nicotine-dependent adult psychiatric inpatients.BackgroundSince the introduction of the smoke-free policy for all psychiatric facilities, a psychiatric admission is likely to upset a nicotine-dependent individual's normal routine of nicotine consumption. In addition to the physiological effects of nicotine withdrawal (NW), the interpersonal dynamic which nurse-led guardianship of nicotine products constructs presents stressors to the nicotine dependent patient.Several systematic reviews evaluating changes in objective measures of agitation amongst smoking patients in medical critical care units have found varied results, with some demonstrating worsening agitation with NRT use. We therefore believe that there is sufficient equipoise in the use of NRT to prompt a review of studies amongst psychiatric inpatients.MethodThis review identified English language studies through developed search strategies in PubMed/MEDLINE, EMBASE, PyschINFO, PSYCHLit, Cochrane databases, and Google scholar. The bibliographies of notable papers were explored. Hand searches of five major psychiatric journals were conducted. Peer reviewed studies of any study design were included if they reported primary data of adult psychiatric inpatients. Studies were extracted from 1990 – present, this was felt appropriate as nicotine replacement patches became available in 1992.Search strategies were informed by MeSH search terms and included multiple conceptions of “agitation”, including variations on; agitation, irritability, and arousal to capture the concept from broad academic constructions. The quality of studies was assessed with the Newcastle-Ottawa and Cochrane Collaboration tools.This review follows PRISMA guidelines, and an application for PROSPERO registration has been submitted pending acceptance.ResultTwo studies were identified which matched inclusion criteria. A double-blinded randomised placebo-controlled trial of 40 nicotine-dependent inpatients from Allen et al. reported a significant 23% reduction in Agitated Behaviour Scores at 24 hours following NRT administration on admission compared to their matched placebo controls. Yet a retrospective cross-sectional analysis from Okoli using scores for NW identified more severe withdrawal symptoms including “restlessness” and “anger/irritability” than nicotine-dependent patients not provided with NRT.ConclusionDespite considerable commentary within literature there is presently only one study providing moderate evidence of a positive benefit to measures of agitated behaviour from the use of NRT amongst nicotine-dependent psychiatric inpatients. There is currently very low evidence whether NRT improves or exacerbates the agitation associated with NW amongst nicotine-dependent psychiatric inpatients.